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Journal of Mind and Medical Sciences
Volume 2 | Issue 2 Article 4
2015
Toxicological Analysis of Some Drugs of Abuse inBiological SamplesAnne Marie CiobanuCarol Davila University of Medicine and Pharmacy
Daniela Luiza BaconiCarol Davila University of Medicine and Pharmacy, [email protected]
Cristian BălălăuCarol Davila University of Medicine and Pharmacy
Carolina NegreiCarol Davila University of Medicine and Pharmacy
Miriana StanCarol Davila University of Medicine and Pharmacy
See next page for additional authors
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Recommended CitationCiobanu, Anne Marie; Baconi, Daniela Luiza; Bălălău, Cristian; Negrei, Carolina; Stan, Miriana; and Bârcă, Maria (2015)"Toxicological Analysis of Some Drugs of Abuse in Biological Samples," Journal of Mind and Medical Sciences: Vol. 2 : Iss. 2 , Article 4.Available at: http://scholar.valpo.edu/jmms/vol2/iss2/4
Toxicological Analysis of Some Drugs of Abuse in Biological Samples
AuthorsAnne Marie Ciobanu, Daniela Luiza Baconi, Cristian Bălălău, Carolina Negrei, Miriana Stan, and Maria Bârcă
This review article is available in Journal of Mind and Medical Sciences: http://scholar.valpo.edu/jmms/vol2/iss2/4
Toxicological analysis of some drugs of abuse in biological
samples
Anne Marie Ciobanu1, Daniela Baconi2, Cristian Bălălău3, Carolina Negrei2, Miriana Stan2, Maria
Bârcă1
1 Carol Davila University of Medicine and Pharmacy, Faculty of Pharmacy, Medicines Control
2 Carol Davila University of Medicine and Pharmacy, Faculty of Pharmacy, Department of Toxicology
3 Carol Davila University of Medicine and Pharmacy, Faculty of General Medicine, St. Pantelimon Hospital
Corresponding author: Daniela Luiza Baconi, e-mail: [email protected]
Running title: Toxicological analysis for drugs abuse
Keywords: toxicological analysis, drugs of abuse, screening test, GCMS, HPLC, LCMS
www.jmms.ro 2015, Vol. II (issue 2): 108- 127.
Date of submission: 2015-03-11; Date of acceptance: 2015-06-17
Abstract
Consumption of drugs of abuse is a scourge of modern world. Abuse, drug addiction and their
consequences are one of the major current problems of European society because of the significant
repercussions in individual, family, social and economic level. In this context, toxicological analysis of
the drugs of abuse in biological samples is a useful tool for: diagnosis of drug addiction, checking an
auto-response, mandatory screening in some treatment programs, identification of a substance in the
case of an overdose, determining compliance of the treatment.
The present paper aims to address the needs of healthcare professionals involved in drugs
addiction treatment through systematic presentation of information regarding their toxicological
analysis. Basically, it is a tool that help you to select the suitable biological sample and the right
collecting time, as well as the proper analysis technique, depending on the purpose of analysis,
pharmacokinetic characteristics of the drugs of abuse, available equipment and staff expertise.
JMMS 2015, 2(2): 108- 127. Review
Toxicological analysis for drugs abuse
109
Introduction
Consumption of drugs of abuse is a scourge of modern world, regardless the fact that we are
talking about high-risk drugs or about the off label use of certain authorized medicinal products. It is a
large-scale, multifactorial, dynamic phenomenon which affects all the age groups, but predominantly the
one between 14 and 35 years old. Abuse and drug addiction, as well as their consequences are one of the
major problems in the current European society (1- 3). This is due to their significant repercussions in
individual, family and social level (crime, social marginalization, and death due to overdose or by
suicide) as well as in the economic level: dependence treatment costs but also the costs of the therapy for
viral and bacterial infections associated with the intravenous consumption (AIDS, HVC, or reappearance
of TBC) (4, 5). Given the major risks associated with the drugs of abuse, their analysis in biological
samples is a useful tool for:
- Initial diagnosis of drug addiction
- Checking an auto-response, a declaration
- Mandatory screening in some treatment programs
- Screening as a method of tracking drug effects over time
- Identification of the substance in case of an overdose
- Determination of treatment compliance
Discussion
Toxicological analysis represents the whole analytical processes through which the presence of a
toxic substance in an analysed sample is determined. It includes the physicochemical methods for the
isolation, identification and quantification of toxic substances in the air, water, soil, food, delict objects
and organic products for the prevention or diagnosis of intoxications (6- 9).
Drugs of abuse are those substances which, as a result of pleasant effects they produce, are used
for other purposes than the ones they are intended to. For example, the therapeutic effect in the
Toxicological analysis for drugs abuse
110
benzodiazepines case or the industrial use in volatile solvents case. Drugs of abuse are those substances
whose possession, transport or storage is restricted by law, due to potential harmful effect on the
consumer and include materials manufactured under license, as well as illicit products manufactured in
clandestine laboratories or natural products (10- 14).
The methodology of toxicological analyses of drugs of abuse is developed based on:
- Type of sample used
- Scope of analysis
- Pharmacokinetic features and biotransformation of the illicit substance
- Available equipment and reagents
- Staff expertise
- Costs.
Biological samples. Depending on the purpose of the analysis, the substances of abuse may be
determined from different biological samples.
Blood/plasma: first choice for the quantitative determination of drugs; therapeutic levels in the blood
are low but, when they are consumed abusively, the concentrations may be 2-3 times higher.
Urine: first choice for screening of drugs of abuse. It is available in sufficient quantity and substances or
metabolites are present in relatively high concentrations.
Hair: it is used for the determination of the history of an abuse substance consumption. Detection is
possible at10-14 days to 90 days after ingestion.
Saliva: it is used for the screening of drugs of abuse consumed within the last 24 hours.
Meconium: reveals maternal history of drugs of abuse consumption in the last 20 weeks of pregnancy
and allow the choice of therapy for mother and new-born.
Toxicological analysis for drugs abuse
111
Breast milk: it is used for the determination of the exposure extent of the infant to drugs of abuse.
For example, in table no. 1 are presented the chromatographic techniques used for the analysis of
methadone cited in the literature, grouped according to biological samples in which the determination is
carried out (15- 16).
Table 1. Chromatographic analysis of methadone according to the biological samples
BIOLOGICAL
SAMPLE GC-MS HPLC LC-MS
Plasma
Schmidt N. et al.,1992
Foster D. et al, 2001
Foster D. et al, 2003
Hallinan R. et al, 2006
Liang H.R. et al., 2004
Whittington D. et al., 2004
Etter M.L. et al., 2005
Lehotay D.C. et al., 2005
Rook E.J. et al., 2005
Quintela O. et al., 2006
Jenkins R. et al., 2006
Shakleya D.M. et al, 2007
Urine Larson M. et al, 2009
Moore C. et al., 2001 Cheng Y.-F. et al., 1999
Dams R. et al, 2003
Shakleya D.M. et al, 2010
Breast milk Choo R.E. et al, 2007
Jansson L.M. et al, 2007
Meconium Choo R. E. et al, 2005
Umbilical cord Nikolaou P.D. et al., 2008 de Castro A. et al., 2009
Placenta Nanovskaya T.N. et al., 2004
Saliva
Concheiro M. et al, 2010
Rodriguez Rosasa M.E. et al.,
2003
Ortelli D. et al., 2000
Hair
Moeller M.R. et al., 1993
Lucas A.C.S. et al., 2000
Girod C. et al., 2001
Kintz P. et al., 2009
Sweating Brunet B.R. et al., 2008
The detection time of abuse substances is varying in different biological samples. For example,
drugs of abuse are detected in saliva within minutes after consumption and in urine only after 4-8 hours
(17- 19).
Biological samples matrix is very complex and contains other endogenous or exogenous
substances in addition to substances of interest. This is the reason that, in most cases, is necessary to use
specific isolation procedures (20- 24).
Toxicological analysis for drugs abuse
112
Table 2. The detection time of certain substances of abuse in saliva and urine
Abuse substance Saliva Urine
Marijuana 12-24 hours Days/wk. Depending on the frequency of use
Opioid 12-24 hours 2-4 days
Amphetamine 24-48 hours 1-2 days
Benzodiazepine 24-48 hours 1 week
Cocaine 12-24 hours 2-3 days
Procedures for extraction of drugs of abuse from biological samples:
The liquid - liquid extraction (LLS): the method used for emergency analysis and for unknown analysis
when substances with physico-chemical properties must be extracted. This process facilitates the
extraction of a drug from aqueous solutions in organic solvents and involves a relatively high
consumption of solvents and multiple operations of extraction and separation.
Solid phase extraction (SPE): the aim of this method is the extraction, purification, and, sometimes, the
concentration of non-volatile or semi-volatile substances for analysis. It involves passing aqueous
solution through a column with silica based desiccant, active carbon and resins. It is a more expensive
process and often less sensitive (25- 29).
Testing of substances of abuse extracted from biological samples
The tests for substances of abuse shall be sub-divided into two types of analytical procedures:
- Screening tests: are quick, simple and requires a minimum previous processing of the sample.
Examples: immunoassays, Thin Layer Chromatography (TLC).
- Confirmatory tests: are performant, sensitive, selective methods that reduce the number of false-
positive / false-negative results. Examples: Gas Chromatography-Mass Spectrometry (GCMS),
High performance liquid chromatography (HPLC), Liquid chromatography-Mass Spectrometry
(LCMS).
Toxicological analysis for drugs abuse
113
1. Screening methods for the determination of drugs of abuse: thin layer chromatography,
immunoassay
For the toxicological screening of drugs of abuse simple, quick and inexpensive analytical methods
are required. Screening methods plays an important role in the forensic medicine laboratories, both in
the analysis of incriminated objects as well as in the analysis of biological samples. Due to the large
diversity of samples it is practically impossible to use extraction methods and sophisticated and time-
consuming instrumental techniques for analysis of all samples. Therefore, it is absolutely necessary to
use simple screening tests to restrict further research area (30- 33).
The conditions that have to be met by a method of analysis to be used as screening test:
- easy to performed
- quick
- not require a complicated and unaffordable equipment
- require few usual reagents
- not require highly qualified personnel
- inexpensive
- able to be performed also outside a lab
- require a minimum processing of the samples.
The interpretation of screening tests results is a complex process, which requires an overview on
limitations raised by the analysis method, by pharmacokinetic and biotransformation characteristics of
the incriminated substance, but also by psychological, physiological and pathological pattern of the
patient (including history of drug dependence) (34). A negative result does not necessarily indicate the
absence of the substance, that can be present but at a level below the detection limit of the method. A
true-positive result from a screening test will not indicate the dose, the time or the route of
administration, and it doesn’t make the difference between an occasional or a chronic administration.
That’s why, it is recommended to use more specific and performant analytical methods for confirming
the screening test results (35- 38).
Toxicological analysis for drugs abuse
114
Screening tests are used in several purposes: forensic (analysis of incriminated samples), clinical or
medical care (admission in substitution treatment, compliance of treatment, testing abstinence during
therapy), occupational medicine, doping tests. The most commonly used screening tests at the present
time are thin-layer chromatography (TLC) and immunoassays.
Thin-layer chromatography (TLC) is a wide spread technique used for the separation and
identification of substances. It is used to analyse bulk active substances, pharmaceutical products, but
also illicit substances or biological samples. Conventional TLC is a fast and low-cost method for
qualitative analysis. Requires a minimum and readily available equipment, and experimental techniques
are easily acquired. These determinations are not expensive, and can be carried out in laboratories with
limited facilities (39- 42).
The Committee of Systematic Toxicological Examination of the International Association of
Forensic Toxicologists (TIAFT), recommends 10 separation systems to identify medicinal substances
and drugs of abuse, depending on their acid-base character. The correspondence between the different
psycho-active substances and TIAFT recommended systems is shown in table number 5.
Table 5. TLC methods for the analysis of psycho-active substances according to TIAFT
Drug of abuse TA TB TC TE TL TAE TAF TAJ TAK TAL
5-methyltryptamine 56 - - - - - - - - -
amphetamine 43 20 9 43 18 12 75 - - -
benzphetamine 73 67 70 87 70 60 - - - -
benzoylecgonine 21 0 1 - - - - - - -
cannabidiol 94 - - 95 - - - 88 76 97
cannabinol 94 - - 95 - - - 90 77 97
cocaine 65 45 47 77 54 35 30 13 0 2
9- THC 11 - - 31 - - - 0 1 31
diamorphine 47 15 38 49 4 26 33 25 5 64
dimethyltryptamine 46 15 10 63 11 14 56 2 3 41
Toxicological analysis for drugs abuse
115
dimethyltryptamine 40 9 9 50 6 14 39 - - -
DOM 51 15 17 41 16 9 76 - - -
ketamine 63 37 63 79 64 68 72 47 4 43
lysergic acid 58 0 0 0 0 70 16 48 7 79
mescaline 20 3 10 24 12 6 63 2 9 51
methamphetamine 31 28 13 42 5 9 63 0 3 45
methadone 48 59 20 77 27 16 60 8 0 45
morphine 37 0 9 20 1 18 23 0 0 15
psilocin 39 5 9 47 9 14 48 - - -
psilocybin 5 0 - 0 0 80 1 - - -
Immunoassays are commonly used as screening tests for testing drugs of abuse. Often, they are
not making any discrimination between the related compounds, so the results obtained are likely to be
cross-reactive. For this reason, such methods are followed by confirmation using performant separation
technique such as GC-MS for qualitative analysis and HPLC for quantitative analysis.
Used on a larger scale, the immunoassays methods are based on the antigen - antibody reaction. The
quality of antibody is critical for the sensitivity, precision and accuracy of the determination. In order to
generate a measurable signal, the immunoassay technique uses a specific antibody for the identified
compound or class of compounds and a labelled form of the same compound or the antibody. The
labelling may be done with a radioisotope in case of radioimmunoassay (RIA), an active enzyme in case
of enzyme-linked immunosorbent assay (ELISA) or a fluorescent compound in case of fluorescence
immunoassay (FIAS) (43- 46). Polarization Immunoassay (FPIA) use fluorescein attached to one
compound (antigen) as marker. When it is bound to antibody, fluorescein molecular rotation slows down
and leads to changes in the polarization of fluorescent emission. The polarization p is inversely
proportional to the concentration of the unbound compound. The main advantage is the exceptional
stability of the FPIA reagents, which enable the tracing of the calibration curve valid for longer time and
the automation of the determination (47).
Toxicological analysis for drugs abuse
116
In the immunoassay methods, the biological sample requires a minimum previous preparation
(e.g. simple centrifugation in the case of urine). After the initial immunoassay test of the screening
program, usually we proceed to identify the particular compound involved using performant separation
methods from complex matrices as biological samples (48- 50).
2. Toxicological examination of the drugs of abuse - confirmatory methods
In order to eliminate false positive or false negative screening tests, toxicological analysis is continued
with confirmatory tests.
Confirmatory tests:
- Are effective methods, sensitive, selective, accurate, reproducible;
- Are performant column chromatographic methods: GC-MS, HPLC, LC-MS;
- Requires a laborious sample preparation stage;
- Requires expensive equipment and highly qualified personnel;
- Are analysed with higher costs.
Chromatography is a method of separating components of a mixture on the basis of their different
distribution between two phases, one of which is stationary - generally fixed on a support (glass or
aluminium plate, paper sheet, steel column, etc.) and other, mobile, which moves in relation to the fixed
phase. This conducted to a different migration of the components leading to their separation. The mobile
phase is gas in GC-MS methods and liquid in HPLC and LC-MS methods. The chromatography is used
both for qualitative and quantitative determination of the chemical substances. The identification is
based on the time required for the migration of the substance into the separation system. The assay is
based on the proportionality of the amount to the peak area (51).
Confirmatory Tests - gas chromatography coupled with mass spectrometry (GC-MS)
The GC-MS is the gold standard for a reliable identification of the drugs of abuse in all kinds of
samples. It combines the advantages of gas chromatography with those of mass-spectrometry. Mass
Toxicological analysis for drugs abuse
117
spectrometry is an analytical technique used to identify organic substances, based on pattern
recognition's of fragments resulting from the ionization.
Table 6. GC-MS methods for heroin and its metabolites analysis in biological samples
References United Nations
International
Drug Control
Programme
Goldberger B. A.
et al.
De Giovanni N. et al.
Wang W.L. et al.
Detected
compounds
Drugs of abuse Heroin, 6-acetyl
morphine
Heroin, cocaine and
metabolites
Cocaine, morphine,
codeine, heroin and
metabolites
Column Diffrent capillary
colum 12 m x 0,2
mm d.i.
Rtx-5, 15m x 25
mm d.i.
HP-1, 12 m x 0,2 mm
d.i.
HP-1, 12 m x 0,2 mm
d.i., film de 0,33 μm
Carrier gas He He ultrapur He
Flow rate 1,9 mL/min 1,2 mL/min 1 mL/min
Injection type splitless splitless
Injector
temperature
250°C 250 °C 250 °C 250 °C
Oven
temperature
150 – 300 °C,
with gradient of
12 °C/min
1 min. to 150 °C,
followed by
increasing to 200 °C
with a gradient of
12.5 °C / min,
maintained at 200
°C for 15 s,
increasing to 290 °C
with 30 °C/min,
held for 4 min
120 °C for 1 min,
increasing to 220 °C
with a gradient of 20 °C
/ min, then to 260 °C
with 5 °C / min and
finally to 280 ° C with a
20 ° C / min, held for 2
min
70 ° for 1 min,
increasing to 220 °C
with a gradient of 35 °C
/ min, constant at 220
°C 0.25 min, increasing
to 250 °C at 10 °C /
min, held at 250 ° C for
3 min
Derivatization SIM or TFA - BSTFA -1%TMCS -
Observation guide of
recommended
methods for
analysing
substances of
abuse
Heroin: LOD 10
μg/L; range 1,0 –
250 μg/L, r 0,995
6-acetyl morphine:
LOD 1,0 μg/L,
range 1,0 – 500
μg/L, r >0,995
LOD 50 ng/mL; range
50-500 ng/mL
Hair: range 0,1 – 10,0
ng/mg
Urine, saliva, plasma:
range 1 – 100 ng/mL
Extraction Liquid-liquid
extraction or SPE
with C18
cartridge
SPE with
ZSDAU020
cartridge
SPE with C18 cartridge SPE
Biological
samples
Blood, saliva and
urine
Blood, plasma,
saliva and urine
Urine Blood, saliva, urine and
hair
Toxicological analysis for drugs abuse
118
The mass spectrum recorded is compared with libraries of mass spectrum. In table number 6 are
listed a few GC-MS methods for heroin and its metabolites analysis in biological samples.
Confirmatory Tests – High Performance Liquid Chromatography (HPLC)
HPLC method is the first choise for the quantitative determination of drugs of abuse in all kinds of
samples. Quantitative determination is based on proportionality between peak area and amount of the
analyte in the sample. In Table number 7 several HPLC methods for analysis of the heroin and its
metabolites in biological samples are presented (52).
Table 7. HPLC methods for analysis of the heroin and its metabolites in biological samples United
Nations
International
Drug Control
Programme
United Nations
International
Drug Control
Programme
Katagi M. et al. Bourquin D. et al. Low A.S. et al. Umans J.
G. et al.
Detected
compound
s
Heroin and metabolites
(monoacetylmorphinae,
diacetylmorphine)
Heroin, morphine,
codeine and their
metabolites
Heroin, 6-
monoacetyl-
morphine,
codeine,
pholcodine,
dihydrocodeine,
morphine
Heroin, 6-
monoacetyl
-morphine,
morphine
Detection UV, λ=218nm Electrochemical Mass spectrometry DAD, λ=210 nm UV, λ=280 nm UV, λ=218
nm
Column LiChrosorb
60, 5 μm,
30cm x 4 mm
d.i.
ODS, 5μm, 25
cm x 4,6 mm d.i.
Capcell Pak SCX 1,5
mm d.i. x 150 mm, 5 μm
C18, 125 x 2 mm
d.i., 3 μm
Hypersil 3μm,
200 x 2 mm d.i.
LiChrosorb
Si 60 5μm,
30 x 4 mm
d.i.,
Faza
mobilă
acetonitril e:
ammonia:
methanol:
acetic glacial
acid soluţia
B
acetonitrile -
0.2M sodium
perchlorate
buffer / 0.005 M
sodium citrate
(1: 9, v / v)
10 mM ammonium
acetate (pH 6.0) -
acetonitrile (30:70, v / v)
o-phosphoric acid,
dicyclohexylamine,
acetonitrile, water,
dichloromethane,
pentane,
methanol,
diethylamine
acetonitrile,
ethanol
concentrate
d ammonia,
methanol,
glacial
acetic acid
Elution Izocratic Izocratic Izocratic Gradient Izocratic Izocratic
Flow rate 1,3 mL/min 1,9 mL/min 0.2 mL/min 0,4 mL/min 80 mL/ora
(1.33
mL/min)
Extracţie LLE or SPE
with C-18
cartridge
LLE or SPE
with C-18
cartridge
SPE ex SPE with C-18
cartridge
SPE with C-18
cartridge
LLE
Biological
samples Blood, saliva
and urine Blood, saliva
and urine Urine PLasma Urine Blood
Confirmation Tests - liquid chromatography coupled with mass spectrometry (LC-MS)
Liquid chromatography coupled with mass spectrometry is a modern hyphenated technique which
combines the advantages of HPLC with those of mass-spectrometry. The mass spectrum recorded is
Toxicological analysis for drugs abuse
119
compared with libraries of mass spectrum. It is used for both qualitative and quantitative determination,
having as advantages the selectivity and the increased sensitivity (53).
In table number 8 a few LC-MS methods for analysis of the methadone and its metabolites in biological
samples are listed (54).
Table 8. LC-MS methods for methadone and its metabolites determination in biological samples
References Vlase L. et
al.
Dams R. et
al.
Danielson T.J.
et al.
Widschwendter
C. G. et al.
Kelly T. et al. Rosas M.E. et al.
Detected
compounds
Methadone Opioids,
cocaine and
metabolites
Methadone and
her metabolites
(EDDP,
EMDP)
Methadone and
quetiapine
Enantiomers
of the
methadone
and of
EDDP,
EMDP
Enantiomers of the
methadone and of
EDDP
Detection MRM (310
→ 265)
SRM MRM MRM (m/z 310
→ 265; 384 →
253)
MRM SIM (m/z 310, 278,
313, 281)
Ionization ESI API ? API API ESI
Column Zorbax SB-
C18 (100 x
3.0 mm, 3.5
μm I.D.)
Synergi Polar
RP (150 x 2
mm, 4 μm)
? Waters
Acquity, C18
(50 x 2,1 mm,
1,7 μm)
AGP alpha-
glicopro-tein
AGP alpha-
glicopro-tein
Internal
standard
- Deuterated
isotopes of
the analysed
compounds
Deuterated
isotopes of the
analysed
compounds
D3-methadone - D3-methadone and
D3-EDDP
Mobile phase Acetonitrile:
0.2% formic
acid 45:55
(v/v)
Mixture of 10
mM
ammonium
formate or
0.001%
formic acid
and
acetonitrilein
various
proportions
Mixture of
acetonitrile and
5 mM formic
acid
20 mM acetic
acid:
isopropanol
93: 7 (v/v)
Acetonitrile:
ammonium acetate
buffer 18:82 (v/v)
Elution isochratic gradient gradient isochratic isochratic
Flow rate 1 mL/min 300 μL/min 0,25 mL/min 0,9 mL/min 0,9 mL/min
Column
temperature
45ºC 25ºC - - - 25ºC
Extraction De-
proteinized
plasma with
methanol
Urine diluted
with water
Without ? With
acetonitrile and
centrifugation
? ?
Biological
samples
Plasma
Urine
Urine Blood
Liver
Urine Hair Saliva
Toxicological analysis for drugs abuse
120
Conclusions
The methodology of a toxicological analysis of the substances of abuse shall be developed on the
basis of: test sample type, analysis purpose, pharmacokinetic and biotransformation particularities of
substance, equipment and reagents available, stuff expertise, cost.
Immunoassays offers a flexible approach of the analyses of drugs of abuse from different
biological samples and represents a convenient method and a quick screening test for a large number of
samples, with different matrixes. A true-positive result of an initial screening test, will not indicate on its
own the dose, the time or the route of administration and it will not make the difference between an
occasional administration or a chronic one.
Screening tests require subsequently performing confirmation tests for removing false positiveâ/
false negative results. Confirmation tests are modern chromatographic techniques (GC-MS, HPLC, LC-
MS), high-performance, sensitive, selective, accurate. Confirmation tests have as disadvantages: time-
consuming step for the processing of the samples, expensive equipment, highly qualified staff and high
cost.
The identification and the assay of drugs of abuse and their metabolites in biological samples
provides to the specialists (doctors, authorities in the field of health, representatives of law) an objective
tool for the diagnostic of abuse or for the monitoring of addictions treatment. Interpretation of the results
is a complex process and requires an overview of: the analysis method, pharmacokinetic and
biotransformation particularities of the substance, clinical pattern of the patient (including history of
drug dependence).
ACKNOWLEDGEMENT: This paper is supported by Sectoral Operational Programme Human
Resources Development (SOP HRD), financed from the European Social Fund and by the Romanian
Government under the contract number POSDRU/159/1.5/S/132395
Toxicological analysis for drugs abuse
121
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